Neurophysiological Effects Induced in the Nervous Tissue by Low-Frequency, Pulsed Magnetic Fields

Summary The influence of pulsed magnetic fields (PMF) on the properties of nervous tissue was investigated. Hippocampal slices or synaptosomes obtained from hippocampal tissue were used as model systems. The amplitude of potentials recorded in vitro from one of the hippocampal pathways (Schaffer collaterals that use glutamate as a neurotransmitter) was employed as a measure of the influence of magnetic fields on synaptic efficiency. The synaptic glutamate turnover and radioactive calcium accumulation were used as markers of the PMF influence on biochemistry of synaptic mechanisms. The exposure of hippocampal slices for 30 min to PMF amplified evoked potentials. While the frequency of 0.16 Hz exerted the strongest effect, lower (0.01, 0.07, 0.03 Hz) and higher (0.5 Hz) frequencies were much less effective. The enhancement of the neuronal excitability was correlated with significant increase in the neuronal spontaneous activity mediated by electrical synapses. The PMF-induced changes in the excitability of the tissue were accompanied by an increase in the synaptic turnover of glutamate. The release of radioactive D-Aspartate (a glutamate analog used as a marker for glutamate turnover) from the slices, and its uptake by synaptosomes were enhanced, and reduced respectively, following the stimulation with pulsed magnetic fields. The frequency which was the most efficient in amplification of evoked potentials (0.16 Hz) was also the most effective in the modulation of the release and uptake processes. The PMF-induced changes in neurotransmitter turnover coincided with an increase in ⁴⁵Ca²⁺ accumulation observed in hippocampal slices exposed to PMF.     

环境雌激素EE2早期慢暴露对雄性大鼠成年后神经发育与空间学习行为的影响

环境雌激素17α-乙炔雌二醇(17alpha-ethynylestradiol, EE2)是一种常见的环境内分泌干扰物,主要经消化道被人和动物摄入,但其对中枢神经系统的影响尚不清楚。为探讨EE2早期慢暴露对Sprague-Dawley (SD)大鼠神经发育和成年后认知行为的影响及其机制,本研究选择5日龄雄性SD大鼠,随机分为3组：空白对照组(Control组)、EE2低剂量组(0.1 μg·kg^-1)、EE2高剂量组(10 μg·kg^-1),每组8只,EE2持续暴露16周。观察大鼠体质量、脑质量变化。采用Morris水迷宫、旷场实验观察大鼠行为学表现。Nissl染色和免疫组织化学染色法观察各组大鼠海马CA1区(CA1)、海马CA3区(CA3)、齿状回(DG)的细胞形态和脑源性神经营养因子(BDNF)的表达,Western Blot检测海马、大脑皮层的IL-1β、IL-10蛋白水平,并测定皮层和海马丙二醛(MDA)含量。结果显示,EE2暴露组大鼠体质量增长速度较对照组减缓,脑质量减轻。行为学发现,EE2组逃逸潜伏期延长,目标象限停留时间、跨台次数减少,中央区运动距离和中央区停留时间减少,并呈剂量依赖性变化。EE2暴露组海马各区神经元排列紊乱、形态不规则,DG区神经元前体细胞数量减少。进一步发现,EE2暴露组大鼠大脑皮层、海马组织的MDA含量均升高,IL-1β表达量增加,IL-10表达量下降。低剂量组海马DG区BDNF表达减少,高剂量组CA1、CA3、DG区BDNF表达均减少。以上结果表明,生命早期0.1 μg·kg^-1 EE2慢暴露可引起雄性大鼠成年后空间学习记忆行为障碍,与海马结构紊乱、BDNF水平降低和脑组织炎症反应有关。     

邻苯二甲酸二丁酯诱导小鼠神经行为学改变及相关生理生化指标分析

探究邻苯二甲酸二丁酯诱导小鼠神经行为学改变及与细胞外调节蛋白激酶(ERK1/2)通路相关蛋白的关联.雄性KM小鼠36只,随机分成4组:生理盐水组、50 mg·kg~(-1)·d~(-1) DBP组、50 mg·kg~(-1)·d~(-1)维生素E(VE)组、DBP+VE组,连续灌胃处理28 d,观察Morris水迷宫结果,检测小鼠脑海马组织的氧化应激(活性氧(ROS)荧光强度、还原型谷胱甘肽(GSH)与丙二醛(MDA)含量)、脑源性神经营养因子(BDNF)、磷酸化cAMP反应元件结合蛋白(p-CREB)、caspase-3水平,Western blot分析ERK1/2及其磷酸化(p-ERK1/2)水平;HE、Nissl染色及Hoechst 33258荧光染色分析脑组织CA1区病理学变化.结果表明,与对照组比较,50 mg·kg~(-1)·d~(-1) DBP组小鼠的学习记忆下降,氧化应激、p-ERK1/2、caspase-3水平上升,BDNF、p-CREB表达下降,差异均有统计学意义(p0.05,p0.01);海马组织CA1病理学损伤及凋亡程度增加.给予抗氧化剂VE处理后,DBP+VE组小鼠的学习记忆上升,氧化应激、p-ERK1/2、caspase-3水平降低,BDNF、p-CREB表达上升,差异均有统计学意义(p0.05);海马组织CA1病理学损伤及凋亡程度降低.由此推测,DBP暴露导致小鼠海马组织CA1病理学损伤、神经元凋亡程度增加、学习记忆下降、其神经行为学改变可以通过添加VE得到缓解,相关生理生化指标测试表明ERK系统应激氧化性损伤机制参与介导了毒理学过程.     

邻苯二甲酸二丁酯影响阿尔茨海默病大鼠学习记忆能力的分子机制研究

为探究邻苯二甲酸二丁酯(DBP)影响阿尔茨海默病(AD)大鼠学习记忆能力的分子机制,将56只SPF级5～6周龄雌性Wistar大鼠随机平均分为7组:阴性对照组、0.25 mg·kg-1·d-1 DBP 组、2.5 mg·kg-1·d-1 DBP 组、25 mg·kg-1·d-1 DBP 组、250 mg·kg-1·d-...     

亚慢性氟暴露致小鼠海马损伤的影响及分子机制研究

为探明亚慢性氟中毒致小鼠海马损伤及分子机制,选用ICR雄性小鼠140只,随机分为对照(C)、低氟(LF)、高氟(HF)、低氟(LF)+L钙离子通道激动剂(FPL)、低氟(LF)+L钙离子通道抑制剂(NIF)、高氟(HF)+激动剂(FPL)、高氟(HF)+抑制剂(NIF) 7组,分别饮用自来水、5、30 mg·L~(-1)氟化钠水溶液90 d,氟染毒第84 d分别腹腔注射生理盐水、FPL64176、Nifedipine7d.同时,采用开场行为及水迷宫检测学习记忆能力;通过HE切片染色观察海马形态结构;根据试剂盒说明检测脑组织谷胱甘肽过氧化物酶(GSH-PX)、总超氧化物歧化酶(SOD)酶活性及丙二醛(MDA)含量;利用RT-PCR和Western Blot法分别检测海马内凋亡相关分子CaMKⅡ和Bax、Bcl-2基因/蛋白表达.结果发现,HF组、LF+FPL组和HF+FPL组小鼠毛发粗糙,暴躁不安.LF、HF组小鼠自发活动、探究行为及空间学习记忆力显著下降(p0.05),海马细胞损伤,SOD、GSH-PX活性极显著下降(p0.01),CaMKⅡ基因/蛋白表达水平显著(p0.05)或极显著(p0.01)上调,Bax基因/蛋白表达水平显著(p0.05)或极显著(p0.01)上调,Bcl-2基因/蛋白表达水平显著(p0.05)或极显著(p0.01)下调,Bax与Bcl-2基因/蛋白表达水平比值显著(p0.05)或极显著(p0.01)上调;LF+FPL、HF+FPL处理加剧了上述基因/蛋白表达水平,LF+NIF、HF+NIF组可逆转上述基因/蛋白表达水平.结果提示,氟中毒致脑损伤与L型钙离子通道及下游相关分子表达异常密切相关,而L钙离子通道抑制剂(Nifedipine)能改善氟暴露造成的海马损伤.     

孕哺期全氟辛烷磺酸染毒对大鼠海马细胞钙稳态的影响

为了阐明孕哺期全氟辛烷磺酸(perfluorooctane sulfonate,PFOS)染毒对大鼠及其仔鼠海马细胞钙稳态的影响,将妊娠Wistar大鼠30只,从妊娠第1天开始对实验组分别以72 mg·kg-1(low,L)、14.4 mg·kg-1(high,H)(以饲料中的PFOS计)的PFOS进行染毒至仔鼠生后3...     

内质网应激介导的凋亡在PBDE-47致大鼠海马损伤中的作用

为了明确内质网应激(endoplasmic reticulum stress,ERS)介导的凋亡在2,2’,4,4’-四溴联苯醚(2,2’,4,4’-tetrabromodiphenylether,PBDE-47)致大鼠神经毒性中的作用,在脑发育的突增期(出生第10天),分别用0 mg·kg~(-1)、1 mg·kg~(-1)、5 mg·kg~(-1)和10mg·kg~(-1)PBDE-47进行单次灌胃染毒,并从出生第8天开始每天给予150 mg·kg~(-1)ERS抑制剂4-苯基丁酸(phenylbutyric acid,PBA),持续3周。仔鼠出生第8周末,从对照组、10 mg·kg~(-1)PBDE-47处理组、150 mg·kg~(-1)PBA处理组和150 mg·kg~(-1)PBA+10mg·kg~(-1)PBDE处理组中随机选取8只大鼠进行水迷宫实验。然后将所有动物断头处死,分离大鼠海马组织,观察其海马组织形态学改变、测定ERS标志分子(GRP78、IRE1和CHOP)和凋亡相关蛋白Cyt c的表达水平。结果显示,10 mg·kg~(-1)PBDE-47处理可导致雌性大鼠海马CA4区细胞排列紊乱、锥形神经细胞数量减少甚至消失,尼氏小体数量减少,大鼠逃避潜伏期延长(P0.05)。5和10 mg·kg~(-1)PBDE-47处理可显著上调ERS相关蛋白IRE1和CHOP的表达水平(P0.05),并明显增强海马组织凋亡相关蛋白Cyt c的表达。PBA干预可明显降低PBDE-47诱导的IRE1和CHOP以及Cyt c蛋白的表达水平,提示PBDE-47可通过ERS介导凋亡,导致大鼠海马组织损伤,从而影响大鼠学习记忆功能。     

不同湿度条件下甲醛暴露致大鼠认知功能损伤及毒理学机制研究

探讨不同湿度条件下甲醛暴露对大鼠认知功能的影响及毒理学机制.取SPF级6～8周龄雌性SD大鼠48只,随机分为6组:对照组(Control组)、甲醛组(FA组)、低湿度组(60％Hum组)、中湿度组(75％Hum组)、高湿度组(90％Hum组)和高湿度联合甲醛组(90％Hum+FA组).不同湿度组分别置于(60％/75％/90％)环境仓中暴露,FA组采用职业气态方式暴露(3 mg·m-3,8 h·d-1,5 d·周-1),连续21 d后观察Morris水迷宫和旷场实验结果,苏木精-伊红染色法(HE)、尼氏染色观察各组大鼠海马神经元的形态学变化,免疫荧光法和免疫印迹实验(Western Blot)检测瞬时受体电位香草素受体4(TRPV4)、闭合蛋白(Occlu-din)和紧密连接蛋白5(Claudin-5)的蛋白表达水平.与Control组相比,不同湿度组和FA组大鼠的认知功能下降,海马神经元数量减少,且随湿度升高而加剧(P＜0.05);与FA组、90％Hum组分别比较,90％Hum+FA组认知功能和海马神经元损伤加剧,且TRPV4表达升高,Occludin和Claudin-5表达降低,差异具有统计学意义(P＜0.05).高湿度和甲醛联合暴露可能通过激活TRPV4离子通道,下调Occludin和Claudin-5表达,加剧大鼠海马神经元的损伤,使认知功能进一步下降.     

全氟辛酸对大鼠海马细胞内钙离子浓度的影响

采用连续灌胃染毒的方法,探讨了全氟辛酸(Perfluorooctanoic acid,PFOA)经口急性染毒对大鼠海马细胞内钙离子浓度的影响.选择雄性Wistar大鼠40只,实验组PFOA染毒剂量分别为2、8、30mg·kg-1(bw).连续灌胃染毒7天后,制备海马单细胞悬液,采用Fura-2/AM荧光探针法测定海马细胞内游离钙离子浓度([Ca2+]i),使用固相萃取-高效液相色谱/质谱联机法(HPLC/MS-MIS)检测血清与脑组织中PFOA浓度.结果表明,染毒组大鼠血清与脑中PFOA浓度均显著高于对照组水平(p<0.01),血清与脑中PFOA浓度之间存在显著的正相关关系(r2=0.611,p<0.01).PFOA染毒8、30mg·kg-1(bw)实验组海马细胞[Ca2+]i分别为(207.89±22.84)nmol·L-1和(284.19±14.75)nmol·L-1,显著高于对照组((141.68±11.47)nmol·L-1)和PFOA染毒2mg·kg-1(bw)实验组((147.38±19.23)nmol·L-1)(p<0.01).大鼠脑、血清中PFOA浓度分别与海马[Ca2+]i存在正相关关系(r2=0.552,p<0.01;r2=0.756,p<0.01).研究结果显示,PFOA暴露可使血清和脑组织中PFOA浓度增加,引起大鼠海马神经元细胞[Ca2+]i升高.     

Neurobiology of the homing pigeon—a review

Homing pigeons are well known as good homers, and the knowledge of principal parameters determining their homing behaviour and the neurological basis for this have been elucidated in the last decades. Several orientation mechanisms and parameters—sun compass, earth’s magnetic field, olfactory cues, visual cues—are known to be involved in homing behaviour, whereas there are still controversial discussions about their detailed function and their importance. This paper attempts to review and summarise the present knowledge about pigeon homing by describing the known orientation mechanisms and factors, including their pros and cons. Additionally, behavioural features like motivation, experience, and track preferences are discussed. All behaviour has its origin in the brain and the neuronal basis of homing and the neuroanatomical particularities of homing pigeons are a main topic of this review. Homing pigeons have larger brains in comparison to other non-homing pigeon breeds and particularly show increased size of the hippocampus. This underlines our hypothesis that there is a relationship between hippocampus size and spatial ability. The role of the hippocampus in homing and its plasticity in response to navigational experience are discussed in support of this hypothesis.